Our overall objective is to understand better how the lung responds to inhaled particles. Since clearance of particles and pathogens from the non-ciliated parenchyma of the lungs is the primary function of the alveolar macrophages and since their migratory pathways and behavior may be pivotal events in the pathogenesis of pulmonary disease, we plan to focus our attention on these cells. This investigation has three distinct purposes: We propose (1) to investigate the origin and differentiation of alveolar macrophages. Using the techniques of histochemistry, autoradiography, and organ culture, we hope to trace the movement of macrophages into and/or through the interstitium and to document their differentiation. We also plan (2) to investigate the consequences of particle ingestion by alveolar macrophages. Whether particle ingestion leads to activation of hydrolytic enzymes and to extracellular enzyme release will be investigated as will the migratory behavior of particle-containing macrophages. Finally, we plan (3) to investigate the importance of competitive phenomena following particle challenge using both in vivo and in vitro test systems. Since inhalation is the primary entry route for agents that cause environmental, occupational, and infectious diseases, it is of clear importance to clarify the roles of the macrophages in alveolar defense and identify environmental and experimental factors that alter macrophage function and cause pulmonary injury. This information will be of value in understanding and controlling environmental hazards. BIBLIOGRAPHIC REFERENCES: Sorokin, S.P. and Brain, J.D. Pathways of Clearance in Mouse Lungs exposed to iron oxide aerosols. Anat. Rec. 181: 581-626, 1975.